Effect of Angiotensin-Neprilysin Inhibition (ARNI) on Prognosis of Chronic Heart Failure

Not Applicable

• Conditions: Chronic Heart Failure
• Interventions: Drug: Entresto; Drug: ACEI/ARB

• Registration Number: NCT03821701
• Lead Sponsor: First Affiliated Hospital Xi'an Jiaotong University

Brief Summary

This study is a randomized controlled multicenter clinical trial, in which about 340 patients with newly diagnosed or prior diagnosed chronic heart will be recruited. Patients will be randomly divided into Angiotensin-Neprilysin Inhibition (ARNI) group and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) group. All-cause death, cardiac death and re-hospitalization due to heart failure will be evaluated in 1, 3, 6, 12 months after recruitment.

Detailed Description

Chronic heart failure is associated with poor prognosis in cardiac patients, although systemic effective drugs has been applied in these patients. European Society of Cardiology (ESC) has recommended ARNI Sacubitril/Valsartan as first-line drugs in replacement of ACEI (I, B) in 2016 for these patients. While American College of Cardiology and The American Heart Association (ACC/AHA) made a first-line recommendation that patients with heart failure due to reduced ejection fraction (HFrEF) could be administrated ARNI directly. Hence, we apply this trial to find if ARNI could replace ACEI/ARB to provide insights for better treatment of chronic heart failure in China. This study is a randomized controlled multicenter clinical trial, in which about 340 patients with newly diagnosed or prior diagnosed chronic heart will be recruited. Patients will be randomly divided into Angiotensin-Neprilysin Inhibition (ARNI) group and ACEI/ARB group. All-cause death, cardiac death and re-hospitalization due to heart failure will be evaluated in 1, 3, 6, 12 months after recruitment. Other safety assessment including left ventricular ejection fraction (LVEF), 6 minutes walk test will be followed up as well.

Study Timeline

• Study Start: 2018-06-01
• Study First Submitted: 2019-01-27
• Study First Submitted QC: 2019-01-28
• Study First Posted: 2019-01-30
• Status Verified: 2019-08
• Last Update Submitted: 2019-08-05
• Last Update Posted: 2019-08-07
• Primary Completion: 2021-01-31
• Study Completion: 2022-01-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 340

Inclusion Criteria

• Age ≥ 18
• HFrEF, defined as LVEF≤40% and New York Heart Association (NYHA) class ≥ II.
• Plasma NT-proBNP ≥ 600 pg/ml, or NT-proBNP ≥ 400 pg/ml if patients have been hospitalized for heart failure in 12 months.
• If patients have been taking ACEI/ARB at recruitment, a stable dose equivalent to at least 10mg/day of enalapril will be required.
• Volunteer for the study and sign the informed consent.

Exclusion Criteria

• Symptomatic hypotension, systolic blood pressure < 95 mmHg at baseline.
• eGFR < 30 ml(/min*1.73m2) at baseline.
• Serum potassium > 5.4 mmol/L at baseline.
• Contraindication of ACEI or ARB.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Newly diagnosed HFrEF ARNI	Entresto	Newly diagnosed HFrEF patients will be administered ARNI Entresto according to the clinical condition among the whole study.
Newly diagnosed HFrEF ACEI/ARB	ACEI/ARB	Newly diagnosed HFrEF patients will be administered ACEI/ARB according to the clinical condition among the whole study.
Prior diagnosed HFrEF ARNI	Entresto	Prior diagnosed HFrEF patients will be administered ARNI Entresto according to the clinical condition among the whole study.
Prior diagnosed HFrEF ACEI/ARB	ACEI/ARB	Prior diagnosed HFrEF patients will be administered ACEI/ARB according to the clinical condition among the whole study.

Primary Outcome Measures

Name	Time	Method
Cardiovascular events	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months	Composite outcomes of all-cause death including cardiac death and re-hospitalization due to heart failure

Secondary Outcome Measures

Name	Time	Method
Six-minutes walking test	Test in 1, 3, 6, 12 months comparing to the baseline.	A test evaluating cardiac function.
LVEF	Test in 1, 3, 6, 12 months comparing to the baseline.	Left ventricular ejection fraction.

Trial Locations

Locations (1)

First Affiliated Hospital of Xi'an Jiaotong University; 🇨🇳 Xi'an, Shaanxi, China